Jablonski P, Howden B O, Baxter K
Monash University, Department of Surgery, Monash Medical Centre, Clayton, Victoria, Australia.
Lab Anim. 2001 Jul;35(3):213-22. doi: 10.1258/0023677011911651.
The objective of this study was to establish an effective post-operative analgesic regimen for Sprague-Dawley (SD) and Dark Agouti (DA) rats. Buprenorphine (0.01 or 0.05 mg/kg), a partial mu opioid agonist, was administered subcutaneously immediately on completion of a standardized surgical procedure, involving anaesthesia, laparotomy and visceral manipulation. Two of the four treatment groups and the saline control group received a second injection 9 h later. Behavioural observations by three independent observers provided no information in assessing pain in this model. All rats lost weight, consumed less food and water after surgery. On the first day, both SD and DA rats receiving buprenorphine lost less weight than untreated control groups. Using weight loss as an efficacy criterion, low-dose buprenorphine, given once or twice, provided effective analgesia in SD rats. A higher single dose provided no additional benefit and a second dose was detrimental, reducing body weight and food intake. In DA rats, the high dose, given twice, appeared to be more effective than the lower dose. All DA cage cohorts consumed < 10% pre-operative food despite buprenorphine treatment, suggesting a higher dosage may be necessary. However, all SD and 80% DA rats who received no buprenorphine gained body weight on the second day, whereas most of the buprenorphine-treated rats continued to lose weight for another 2 days, despite increased food consumption by both strains. Buprenorphine may adversely affect intestinal function over a number of days due to its enterohepatic circulation; this effect may be more severe in DA rats. Adverse metabolic effects of buprenorphine and other opioids may preclude their use in the future if it can be shown that non-steroidal anti-inflammatory drugs (NSAIDs) provide equally effective analgesia.
本研究的目的是为斯普拉格-道利（SD）大鼠和黑褐大鼠（DA）建立一种有效的术后镇痛方案。在完成包括麻醉、剖腹术和内脏操作的标准化手术后，立即皮下注射0.01或0.05毫克/千克的丁丙诺啡（一种部分μ阿片受体激动剂）。四个治疗组中的两个组以及生理盐水对照组在9小时后接受第二次注射。由三名独立观察者进行的行为观察在评估该模型中的疼痛方面没有提供任何信息。所有大鼠术后体重减轻，食物和水摄入量减少。第一天，接受丁丙诺啡治疗的SD大鼠和DA大鼠体重减轻均少于未治疗的对照组。以体重减轻作为疗效标准，低剂量丁丙诺啡单次或两次给药可在SD大鼠中提供有效的镇痛作用。较高的单次剂量没有额外益处，第二次给药则有害，会降低体重和食物摄入量。在DA大鼠中，高剂量两次给药似乎比低剂量更有效。尽管接受了丁丙诺啡治疗，但所有DA笼养组的术前食物摄入量均<10%，这表明可能需要更高的剂量。然而，所有未接受丁丙诺啡治疗的SD大鼠和80%的DA大鼠在第二天体重增加，而大多数接受丁丙诺啡治疗的大鼠尽管两种品系的食物摄入量均增加，但在接下来的2天仍继续体重减轻。由于丁丙诺啡的肠肝循环，其可能在数天内对肠道功能产生不利影响；这种影响在DA大鼠中可能更严重。如果能证明非甾体抗炎药（NSAIDs）能提供同样有效的镇痛作用，那么丁丙诺啡和其他阿片类药物的不良代谢作用可能会使其在未来无法使用。
